Surrogate Endpoints in Drug Development: A Review of Statistical and Regulatory Perspectives and Applications

ABSTRACT A surrogate endpoint is an endpoint that is used as a substitute for a direct clinical outcome measure of how a patient feels, functions, or survives. The use of surrogate endpoints offers potentially significant ethical, logistical, and/or economic advantages to clinical studies, thereby deserving serious consideration in clinical development planning. The means of establishing a biomarker as a validated or reasonably likely s urrogate endpoint requires scientific evidence of the predictive nature of a potential surrogate endpoint and statistical validation of the predictivity of the surrogate endpoint on clinical outcome measures. In this review, we present statistical methodologies and regulatory considerations for establishing surrogate endpoints and provide a few applications across multiple disease areas.